Genetic Risk for Schizophrenia Linked to Mother's Age

The known association between increased schizophrenia risk and a mother's age at her first child's birth appears to have at least a partial genetic component, suggests new research in JAMA Psychiatry.

Past research has previously identified a link between risk of psychiatric disorders and older fathers, and emerging evidence suggests a similar risk in children of younger or older mothers. However, “it is unclear if risk to offspring is due to psychosocial, lifestyle or biological aging factors associated with maternal age or if women at higher risk for schizophrenia tend, on average, to have their first child at an earlier or later age,” wrote Divya Mehta, PhD, of the University of Queensland in Brisbane, Australia, and colleagues.

The researchers used a whole-genome analysis method to compare genotypes of two unrelated groups, thereby removing confounding factors typically present in other case-control studies that investigate potential genetic contributions to a condition. One group was a cohort of 12 247 women from Estonia, the Netherlands, Sweden and the United Kingdom whose genotypes were analyzed with regards to their ages when they first gave birth.

The other genotyped cohort came from a case-control study involving 18 957 individuals with schizophrenia and 22 673 controls. This study had previously shown an association between schizophrenia risk and having an older mother.

By comparing both groups, the researchers sought to identify potential similarities in genetic factors between those with schizophrenia and mothers who first gave birth at older ages, independent of partners' ages and the latter mothers' psychiatric health.

Through a series of multiple analyses, the researchers determined that “a significant overlap between genetic factors associated with risk of schizophrenia and genetic factors associated with age at first birth” existed. Women with the greatest genetic risk for schizophrenia, then, generally have first children at earlier or later ages than the average in the general population, regardless of the women's partners' ages.

“A caveat of our findings is that the genetic association between risk of schizophrenia and delayed age at first birth was only marginally significant given the number of analyses performed, perhaps reflecting smaller sample size and correspondingly larger standard errors for women with delayed age at first birth, and so require replication in a larger sample,” the authors noted.

If confirmed, “it has important implications because it implies that risk of schizophrenia associated with increased age in mothers is not entirely due to the father's age.”

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